| In multicellular organisms, the oncogene Akt acts to promote cell survival, and is activated by PI(3,4,5)P3. The tumor suppressor PTEN acts in opposition to Akt by dephosphorylating PI(3,4,5)P3 to PI(4,5)P2. Both genes have strong homologs in yeast, although yeast do not produce the PI(3,4,5)P 3 phospholipid that connects Akt and PTEN. In yeast, SCH9 is believed to be an Akt homolog with phenotypes impinging on longevity, stress resistance, and nutrient sensing. TEP1 is a PTEN homolog, and has not been previously studied. We attempted to determine whether mammalian Akt could functionally substitute for yeast SCH9, and investigated the function of TEP1.; Expression of Akt in wild type yeast and yeast heterozygous for an SCH9 deletion did not affect cell size or growth rate when compared to expression of a kinase-incompetent control. Expression of Akt increased the heat stress resistance of both wild type and heterozygous SCH9/sch9 strains; this is contrary to what might be expected were these genes functional homologs. The effects of Akt expression on longevity were indeterminate. Therefore, we conclude that Akt is not a functional homolog of SCH9 in Saccharomyces cerevisiae.; TEP1 deletion had no significant effect in haploid yeast. TEP1 deletion in diploids conferred resistance to the PI3K-inhibitor wortmannin, and to lithium ions, indicating that Tep1p most likely acts upon phospholipids as its major substrate. Homozygous tep1 yeast initiate and complete meiosis, but there is a defect in the trafficking or deposition of dityrosine, a major component of the spore wall. Introduction of a PTEN mutation commonly found in human tumors to the analogous position of TEP1 produces a nonfunctional protein based on in vivo activity. These results imply that TEP1, like its mammalian counterparts, acts in the phosphatidyinositol pathway in S. cerevisiae. |
